Acute or chronic treatment of rats, mice and hamsters with cobaltous chloride produced up to 200% increase in hepatic glutathione (GSH). GSH levels in lung, kidney and ileum are also markedly elevated. GSH levels are significantly elevated within 4-8 hrs after a single sub-levels after 8 hrs. Thus, studies using cobaltous chloride as a tool to implicate cytochrome P-450 in chemical toxicities in vivo must be interpreted with caution, since GSH is known to participate in the detoxication of certain toxic, electrophilic metabolites.